crossing96/oncoscreening huggingface dataset:
Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches.	With the mechanistic understanding of immune checkpoints and success in checkpoint blockade using antibodies for the treatment of certain cancers, immunotherapy has become one of the hottest areas in cancer research, with promise of long-lasting therapeutic effect. Currently, however, only a proportion of cancers have a good response to checkpoint inhibition immunotherapy. Better understanding of the cancer response and resistance mechanisms is essential to fully explore the potential of immunotherapy to cure the majority of cancers. Bladder cancer, one of the most common and aggressive malignant diseases, has been successfully treated both at early and advanced stages by different immunotherapeutic approaches, bacillus Calmette-Guérin (BCG) intravesical instillation and anti-PD-1/PD-L1 immune checkpoint blockade, respectively. Therefore, it provides a good model to investigate cancer immune response mechanisms and to improve the efficiency of immunotherapy. Here, we review bladder cancer immunotherapy with equal weight on BCG and anti-PD-1/PD-L1 therapies and demonstrate why and how bladder cancer can be used as a model to study the predictors and mechanisms of cancer immune response and shine light on further development of immunotherapy approaches and response predictive biomarkers to improve immunotherapy of bladder cancer and other malignancies. We review the success of BCG and anti-PD-1/PD-L1 treatment of bladder cancer, the underlying mechanisms and the therapeutic response predictors, including the limits to our knowledge. We then highlight briefly the adaptation of immunotherapy approaches and predictors developed in other cancers for bladder cancer therapy. Finally, we explore the potential of using bladder cancer as a model to investigate cancer immune response mechanisms and new therapeutic approaches, which may be translated into immunotherapy of other human cancers. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.	bladder
Improving the Timely Detection of Bladder and Kidney Cancer in Primary Care.	Bladder and kidney cancer are the 10th and 7th most common cancers in the United Kingdom (UK). They present with symptoms that are typically investigated via the same diagnostic pathway. However, diagnosing these cancers can be challenging, especially for kidney cancer, as many of the symptoms are non-specific and occur commonly in patients without cancer. Furthermore, the recognition and evaluation of these symptoms may differ because of the lack of supporting high-quality evidence to inform management, a problem also reflected in currently ambiguous guidelines. The majority of these two cancers are diagnosed following a referral from a general practitioner. In this article, we summarise current UK and United States (US) guidelines for investigating common symptoms of bladder and kidney cancer-visible haematuria, non-visible haematuria and urinary tract infections. Our article aims to support clinicians in recognising and investigating patients with symptoms of possible bladder and kidney cancer in a timely fashion. We discuss challenges during the diagnostic process and possible future interventions for improvement.	bladder
KMT2D inhibits the growth and metastasis of bladder Cancer cells by maintaining the tumor suppressor genes.	KMT2D, a kind of histone H3 lysine 4 (H3K4) methyltransferase, its abnormal expression confirmed to be associated with diverse tumors, but is lack of defined role in bladder cancer (BC). KMT2D mutation was analyzed using several databases. Immunohistochemistry and clinicopathological analysis of KMT2D in 51 paired of BC tissues and corresponding normal tissues were used to evaluate the relationship between KMT2D and BC. The effects of silencing or over-expressing KMT2D on HTB-9 and T24 cell viability, migration and invasion were performed using MTT, wound scratch and Transwell, respectively. Also, bladder cancer mouse model was established by hypodermic injection of the BC cells. Associated expressions of methylation genes, oncogenes and tumor suppressors were assessed by western blot and quantitative real-time PCR. KMT2D was frequent mutation in various tumors, including BC. It was negative expression in BC tissues and cells, also implicated with tumor stages and lymph node metastasis. In silencing KMT2D HTB-9 and T24 cells, cell viability, migration and invasion were notably promoted. Meanwhile, knockdown of KMT2D benefited to solid tumor formation in vivo. However, over-expressing KMT2D represented contrary results. Especially, KMT2D over-expression induced the activity of H3K4 monomethylation (me1), and effectively enhanced PTEN and p53 expressions as well as repressed STAG2 expression. Meanwhile, KMT2D had no obvious effect on Survivin. This work suggested an anti-tumor role for KMT2D in vitro and in vivo, as well as provided a possible tumor inhibition mechanism in which KMT2D enhanced H3K4me1 activity to support the expressions of tumor suppressors.	bladder
Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial.	BACKGROUND: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer. OBJECTIVE: To assess the performance of BE for NMIBC recurrence. DESIGN, SETTING, AND PARTICIPANTS: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age ≥22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10ml of urine, and able to consent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology. RESULTS AND LIMITATIONS: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively. CONCLUSIONS: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced. PATIENT SUMMARY: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens.	bladder
Staging the Host: Personalizing Risk Assessment for Radical Cystectomy Patients.	CONTEXT: Perioperative and long-term functional and oncologic outcomes following radical cystectomy (RC) for localized bladder cancer remain unchanged despite advances in technique and perioperative management, as well as neoadjuvant and adjuvant therapy. Accurate assessment of a patient's perioperative risk is critical to inform preoperative counseling and determine a patient's fitness for RC. OBJECTIVE: To review and synthesize conventional and novel objective patient-specific risk assessment tools that may be incorporated into clinical practice for perioperative risk prognostication with respect to both postoperative complications and long-term oncologic outcomes, patient counseling, and decision-making when RC is being considered. EVIDENCE ACQUISITION: A collaborative review was performed to synthesize currently available evidence on comorbidity, age, body composition, nutrition, frailty, and geriatric assessments for patients undergoing RC. EVIDENCE SYNTHESIS: Current guidelines recommend that pre-RC risk assessment should take into account age, performance status, and comorbidity. However, conventional comorbidity indices perform inconsistently in accurate assessment of the risk of perioperative complications, prolonged rehabilitation, and long-term oncologic outcomes. Novel metrics including standardized assessments of dependency, comorbidity severity, sarcopenia, malnutrition, physical and cognitive frailty, and comprehensive geriatric assessments may offer more precise estimates of physiologic age and relative vulnerability to adverse outcomes following RC. CONCLUSIONS: Perioperative risk assessment before RC should incorporate objective measures of physiologic age, physical function, nutrition, lean muscularity, and frailty. The use of standardized multidimensional instruments should be encouraged for patients undergoing consideration for RC to identify potentially modifiable risk factors that can be targeted with prehabilitation interventions. Future work is needed to validate the performance of these metrics with respect to predicting perioperative complications and oncologic outcomes and to define and assess the effectiveness of specific prehabilitation interventions to optimize patients before surgery. PATIENT SUMMARY: We review several metrics that doctors can use to measure the risks associated with bladder removal, a major surgical procedure. Moving beyond evaluating a patient's age, the burden of other health problems, and surgeon intuition, these tools may be used to counsel patients regarding their surgical risk, to predict oncologic outcomes, and to help identify potential interventions to improve surgical readiness.	bladder
Urinary markers in the surveillance of non-muscle invasive bladder cancer. A literature review.	"BACKGROUND: The surveillance of non-muscle-invasive bladder cancer (NMIBC) is usually performed by cystoscopy and cytology. Until today, no effective urinary biomarker has been used to reduce the morbidity and cost associated with these procedures. OBJECTIVE: To describe the performance of urinary biomarkers in the surveillance of NMIBC. EVIDENCE ACQUISITION: on August 1, 2018, a bibliographic search was carried out in Pubmed, Embase and Cochrane Library, limited to the last 10 years, with the terms: bladder cancer, recurrence, detection and urine marker.973 registers were obtained, and 27 publications were selected following the PRISMA recommendations. EVIDENCE SYNTHESIS: The negative predictive values (NPV) of several assays could reduce the number of cystoscopies in NMIBC surveillance. Six transcription-factor trials had an NPV rate greater than 90%, and one of them can be performed at the control point. Six transcription-factors evaluations describe anticipated diagnosis between 68% and 83% of their ""false positives"". Two transcription factors and one protein assays proved reduction between 23% and 35% of surveillance cystoscopies. Nowadays, cell-based assays are restricted to reflex test after doubtful cytologies. CONCLUSION: There are few studies analysing the improvement of the NMIBC surveillance protocols. Several transcription factor assays are more precise and allow anticipatory diagnosis. Currently, there are no comparative studies between alternative surveillance protocols and classic ones."	bladder
KIF20A Affects the Prognosis of Bladder Cancer by Promoting the Proliferation and Metastasis of Bladder Cancer Cells.	OBJECTIVE: To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients. METHODS: Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot. Immunohistochemical (IHC) staining was used to identify the expression and distribution of KIF20A proteins in the tissue samples. The relationship between the KIF20A expression and the clinical pathology of bladder cancer was analysed. The effect of the differential expression of KIF20A on the prognosis of patients with bladder cancer was analysed by the TCGA database. The plasmid was transfected into the bladder cell lines T24 and 5637 to construct two stable cell lines with knocked down KIF20A. The effect of KIF20A expression on the proliferation and invasion of T24 and 5637 bladder cells was explored in vitro using the abovementioned stable cell lines. The effect of the KIF20A expression on the proliferation of bladder cancer cells was evaluated by a mouse xenograft model. RESULTS: The expression of KIF20A was significantly higher in the bladder cancer tissues than in the adjacent control tissues. The expression of KIF20A was significantly associated with the degree of pathological differentiation of bladder cancer. Patients with a higher expression of KIF20A had a higher tumour grade and a more advanced stage. The mean survival of patients with a high KIF20A expression was significantly lower than the mean survival of patients with a low KIF20A expression. The in vitro experiments demonstrated that the knockdown of KIF20A significantly inhibited T24 and 5637 cell proliferation and invasion. The in vivo experiments showed that the knockdown of KIF20A significantly inhibited the proliferation of the bladder tumours. CONCLUSION: KIF20A promotes the proliferation and metastasis of bladder cancer cells. Bladder cancer patients with a high KIF20A expression have a worse tumour differentiation and a poor prognosis. KIF20A may become an independent factor that affects the prognosis of bladder cancer patients and a therapeutic target for bladder cancer.	bladder
The Pathological Significance and Prognostic Roles of Thrombospondin-1, and -2, and 4N1K-peptide in Bladder Cancer.	BACKGROUND/AIM: Thrombospondins (TSPs) play a role as inhibitors of angiogenesis under various pathological conditions. The aim of the study was to evaluate the pathological significance and prognostic role of the 4N1K-peptide (KRFYVVMWKK), which is derived from TSP-1 and -2, in bladder cancer. MATERIALS AND METHODS: Two-hundred and six bladder cancer tissues were examined for expression of TSP-1, TSP-2, and 4N1K-peptide by immunohistochemistry. Cancer cell proliferation, apoptosis, angiogenesis and matrix metalloproteinase (MMP)-9 immunoreactivity were also examined. RESULTS: Expression of TSP-2 and 4N1K-peptide was negatively associated with T stage, metastasis, and grade. TSP-2 expression was negatively associated with cancer cell proliferation and MMP-9 expression, whereas 4N1K-peptide was significantly associated with apoptosis, angiogenesis, and MMP-9 expression. Multivariate analysis showed that 4N1K-peptide expression was a significant predictor of metastasis (hazard ratio=3.90, p=0.002). CONCLUSION: TSP-2 and 4N1K peptide played important roles in malignant aggressiveness and progression of bladder cancer via complex mechanisms involving cell proliferation, apoptosis, angiogenesis, and MMP-9.	bladder
Social Determinants of Appropriate Treatment for Muscle-Invasive Bladder Cancer.	BACKGROUND: Racial disparities in guideline-based, appropriate treatment (ApT) may be a significant driving force for differences in survival for people with nonmetastatic muscle-invasive bladder cancer (MIBC). We hypothesize that receipt of ApT is influenced by factors such as race and socioeconomic status, irrespective of neighborhood-level differences in healthcare, variations in practice patterns, and clinical characteristics of patients with nonmetastatic MIBC. METHODS: Within the National Cancer Database, we identified individuals diagnosed with MIBC between 2004 and 2013. Multivariable logistic regression and mixed effects modelling was used to examine predictors of ApT, clustered within institutions. RESULTS: A total of 51,350 individuals had clinically staged nonmetastatic, lymph node-negative MIBC. Black individuals comprised 6.4% of the cohort. Mean age was 72.6 years (SD 11.6) with a male predominance (71.4%). Less than half received ApT (42.6%). Fewer black individuals received ApT compared with white individuals (37% vs. 43%, P < 0.001). When clustered by institution, the odds of ApT were 21% lower for black individuals [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.73-0.87] compared with white individuals with nonmetastatic MIBC. When restricted to higher volume centers with more diverse populations, black individuals had 25% lower odds of ApT (OR, 0.75; 95% CI, 0.61-0.91; P < 0.01), compared with white counterparts. CONCLUSIONS: Racial disparities in treatment persisted after accounting for various clinical factors and social determinants of health. Future efforts should focus on addressing racial bias to improve disparities in bladder cancer treatment. IMPACT: If we are not delivering evidence-based care due to these biases (after accounting for access and biology), then it is expected that patients will experience inferior outcomes.	bladder
Synthesis and Evaluation of Boronated Chitosan as a Mucoadhesive Polymer for Intravesical Drug Delivery.	This work reports the synthesis of boronated chitosan by reacting it with 4-carboxyphenylboronic acid to improve its mucoadhesive properties. Three products with differing extent of boronate conjugation were synthesized and characterized using (1)H NMR, FT-IR, and UV-Vis spectroscopy, and the potential of these polymers to extend the residence time of loaded model drug in the bladder was investigated. (1)H NMR and ninhydrin test were used to evaluate the extent of chitosan modification. Mucoadhesive properties were evaluated using ex vivo flow-through technique on porcine bladder mucosal tissue combined with fluorescent microscopy, where fluorescein sodium was used as a model drug. The mucoadhesive properties of these polymers on porcine bladder mucosa were also studied using tensile test. There was good correlation in the mucoadhesive profiles of the polymers using the flow through and tensile techniques. The degree of chitosan modification had a remarkable influence on their mucoadhesive behavior, and greater mucoadhesion was observed with increased degree of boronation. These chitosan derivatives have the potential as intravesical drug delivery systems to improve bladder therapy.	bladder
Preoperative predictors of early death risk in bladder cancer patients treated with robot-assisted radical cystectomy.	"BACKGROUND: Early identification of early death for bladder cancer patients undergoing radical cystectomy based on the laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for bladder cancer patients. METHODS: A total of 186 bladder cancer patients who underwent robot-assisted radical cystectomy (RARC) were identified between October 2014 and May 2017. The probability of dying within 1 year after RARC was defined as the end point ""early death."" Predictive factors including clinical features and laboratory findings at diagnosis were retrospectively collected. RESULTS: Median follow-up time after RARC was 20.6 months (1.2-43.7 months). Fifty-one patients (27.4%) died during follow-up and 31 within 1 year from surgery (1-year mortality rate: 16.7%). All potentially prognostic factors were assessed on univariate analyses, which revealed the following factors as being associated with higher risk of early death within 1 year after RARC: older age (P = 0.004), advanced clinical stage (P = 0.005), presence of hydronephrosis (P = 0.021), higher fibrinogen (P = 0.007), higher PLR (P = 0.031), and lower PNI (P = 0.016). In a multivariate Cox proportional hazard regression model analysis, age >60 years (HR = 7.303, 95% CI 1.734-30.764; P = 0.007) and fibrinogen ≥3.295 g/L (HR = 2.396, 95% CI 1.138-5.045; P = 0.007) at diagnosis were independent prognostic factors of early death after RARC. CONCLUSION: Age and preoperative elevated plasma fibrinogen level were independent predictors for 1-year mortality after RARC. We believe that plasma fibrinogen levels may become a useful biomarker, which may help guide the treatment decision-making process for patients with bladder cancer."	bladder
Synthesis and biological evaluation of quercetin-zinc (II) complex for anti-cancer and anti-metastasis of human bladder cancer cells.	Bladder cancer is the 13th leading cause of cancer death worldwide, and its mortality rate is highly associated with the motility of the malignant cells. Although the techniques of urothelial cancer treatment have been continuously advanced in the last decade, the invasive bladder cancer remains incurable and the mean survival time of the patients with high-grade malignancy after cancer relapse is still < 6 months, indicating a new strategy which can reduce bladder cancer cell motility and/or progression is urgently needed. Quercetin is a polyphenolic flavonoid with approved anti-tumor effect. However, the drawbacks of quercetin, including low absorption, extensive metabolism, and rapid elimination, severely hamper its availability in the clinic. In this study, we aim to synthesize the quercetin-zinc complex (Q-ZnCPX) and explore its anti-cancer and anti-metastasis efficacies on human bladder cancer cells in vitro. Based on the results of cell movement and protein expressions in BFTC-905 cells, we found that both cell migratability and invasiveness were markedly reduced by the Q-ZnCPX with concentration of ≥ 12.5 μM through p-AKT and MT1-MMP regulations compared to the cells without treatment (P < 0.05). Moreover, the synthesized Q-ZnCPX with ≥ 75 μM can even provide > 50% of mortality rate (P < 0.05) to the cancer cell after 24-h treatment. These results demonstrated that the synthetic Q-ZnCPX may serve as feasible tool for both anti-cancer and anti-metastasis on human bladder cancer cells dependent on the dosage.	bladder
Anti-PD-1 Immunotherapy-Induced Flare of a Known Underlying Relapsing Vasculitis Mimicking Recurrent Cancer.	Safe use of immune checkpoint blockade in patients with cancer and autoimmune disorders requires a better understanding of the pathophysiology of immunologic activation. We describe the immune correlates of reactivation of granulomatosis with polyangiitis (GPA)-an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis-in a patient with metastatic urothelial carcinoma treated with pembrolizumab. After PD-1 blockade, an inflammatory pulmonary nodule demonstrated a granulomatous, CD4+ T-cell infiltrate, correlating with increased CD4+ and CD8+ naïve memory cells in the peripheral blood without changes in other immune checkpoint receptors. Placed within the context of the existing literature on GPA and disease control, our findings suggest a key role for PD-1 in GPA self-tolerance and that selective strategies for immunotherapy may be needed in patients with certain autoimmune disorders. We further summarize the current literature regarding reactivation of autoimmune disorders in patients undergoing immune checkpoint blockade, as well as potential immunosuppressive strategies to minimize the risks of further vasculitic reactivation upon rechallenge with anti-PD-1 blockade. KEY POINTS: Nonspecific imaging findings in patients with cancer and rheumatological disorders may require biopsy to distinguish underlying pathology.Patients with rheumatologic disorders have increased risk of reactivation with PD-(L)1 immune checkpoint blockade, requiring assessment of disease status before starting treatment.Further study is needed to evaluate the efficacy of treatment regimens in preventing and controlling disease reactivation.	bladder